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Types of Cancer Stem Cells

  • Gautham Chengizkhan
  • Bharti Bisht
  • Sridhar Muthusami
  • Muralidharan Anbalagan
  • Ilangovan Ramachandran
  • R. Ileng KumaranEmail author
Chapter
  • 73 Downloads

Abstract

The discovery of cancer stem cells (CSCs) has revolutionized the field of cancer biology due to the intrinsic role of CSCs in the initiation, progression or relapse of cancers. The identification of different types of CSCs has given a great opportunity to researchers and clinicians, to understand the basic biology of various types of CSCs or cancers, and has also added an extra dimension in the development of innovative approaches or therapeutics to specifically target CSCs. The morbidity and mortality caused by various cancers have started to decline rapidly in the past couple of decades. Furthermore, the life expectancy of cancer patients have increased with the invention of modern state-of-the-art technologies, besides rapid advances in the development and preclinical testing of new drugs that target CSCs. Additionally, more insights into the molecular biology of CSCs was made possible, when unique cell markers, which are specific to a particular type of tumor was deciphered. Importantly, the characterization and evaluation of key signalling pathways in CSCs are critical, as emerging evidence indicate that CSCs play a key role in dissemination during cancer metastasis or relapse. In this chapter, we discuss about CSCs that are specific to ovarian, thyroid, melanoma and pancreatic cancers. We also discuss about the key CSC signalling pathways, as understanding them will advance the therapeutic strategies, or evaluation of efficacy of novel CSC-targeting drugs that could be used in the treatment of cancer patients.

Keywords

Cancer stem cells (CSCs) Cell surface markers Drug targets Ovarian cancer stem cells (OCSCs) Thyroid cancer stem cells (TCSCs) Melanoma cancer stem cells (MCSCs) Pancreatic cancer stem cells (PCSCs) CSC signalling pathway Hedgehog (Hh) Notch Wingless-type (Wnt)/β-catenin Transforming growth factor-β (TGF-β) Nuclear factor-κB (NF-κB) Insulin-like growth factor 1 (IGF1) Cluster of differentiation (CD) 

Notes

Acknowledgments

We gratefully thank Dr. Yuvaraj Sambandam (Northwestern University, Feinberg School of Medicine, USA) for his critical reading and comments on this book chapter.

Conflict of interest: The authors declare no conflict of interest.

References

  1. 1.
    Prager BC, Xie Q, Bao S, Rich JN (2019) Cancer stem cells: the architects of the tumor ecosystem. Cell Stem Cell 24(1):41–53CrossRefGoogle Scholar
  2. 2.
    Nazio F, Bordi M, Cianfanelli V, Locatelli F, Cecconi F (2019) Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications. Cell Death Differ 26(4):690–702CrossRefGoogle Scholar
  3. 3.
    Najafi M, Farhood B, Mortezaee K (2019) Cancer stem cells (CSCs) in cancer progression and therapy. J Cell Physiol 234(6):8381–8395CrossRefGoogle Scholar
  4. 4.
    Lee G, Hall RR III, Ahmed AU (2016) Cancer stem cells: cellular plasticity, niche, and its clinical relevance. J Stem Cell Res Ther 6(10):363CrossRefGoogle Scholar
  5. 5.
    Batlle E, Clevers H (2017) Cancer stem cells revisited. Nat Med 23(10):1124–1134CrossRefGoogle Scholar
  6. 6.
    Wang Z, Zöller M (2019) Exosomes, metastases, and the miracle of cancer stem cell markers. Cancer Metastasis Rev 38(1–2):259–295CrossRefGoogle Scholar
  7. 7.
    Papaccio F, Paino F, Regad T, Papaccio G, Desiderio V, Tirino V (2017) Concise review: cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Transl Med 6(12):2115–2125CrossRefGoogle Scholar
  8. 8.
    Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A, Siegel RL (2018) Ovarian cancer statistics, 2018. CA Cancer J Clin 68(4):284–296CrossRefGoogle Scholar
  9. 9.
    Kechin AA, Boyarskikh UA, Ermolenko NA, Tyulyandina AS, Lazareva DG, Avdalyan AM, Tyulyandin SA, Kushlinskii NE, Filipenko ML (2018) Loss of heterozygosity in BRCA1 and BRCA2 genes in patients with ovarian cancer and probability of its use for clinical classification of variations. Bull Exp Biol Med 165(1):94–100CrossRefGoogle Scholar
  10. 10.
    Kryczek I, Liu S, Roh M, Vatan L, Szeliga W, Wei S, Banerjee M, Mao Y, Kotarski J, Wicha MS, Liu R (2012) Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells. Int J Cancer 130(1):29–39CrossRefGoogle Scholar
  11. 11.
    Chen HZ, Wang LJ, Lu HW, Chen Q, Di N, Lin ZQ (2012) Expression and functional role of ALDH1 in cervical carcinoma cells. Asian Pac J Cancer Prev 13:1325–1331CrossRefGoogle Scholar
  12. 12.
    Guo Z, Hardin H, Lloyd RV (2014) Cancer stem-like cells and thyroid cancer. Endocr Relat Cancer 21(5):T285–T300CrossRefGoogle Scholar
  13. 13.
    Carr S, Smith C, Wernberg J (2020) Epidemiology and risk factors of melanoma. Surg Clin 100(1):1–2CrossRefGoogle Scholar
  14. 14.
    La Porta C (2009) Cancer stem cells: lessons from melanoma. Stem Cell Rev Rep 5(1):61–65CrossRefGoogle Scholar
  15. 15.
    Zhang Q, Zeng L, Chen Y, Lian G, Qian C, Chen S, Li J, Huang K (2016) Pancreatic cancer epidemiology, detection, and management. Gastroenterol Res Pract 2016:1Google Scholar
  16. 16.
    Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67(3):1030–1037CrossRefGoogle Scholar
  17. 17.
    Zhan HX, Xu JW, Wu D, Zhang TP, Hu SY (2015) Pancreatic cancer stem cells: new insight into a stubborn disease. Cancer Lett 357(2):429–437CrossRefGoogle Scholar
  18. 18.
    Hu L, McArthur C, Jaffe RB (2010) Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant. Br J Cancer 102(8):1276–1283CrossRefGoogle Scholar
  19. 19.
    Stewart JM, Shaw PA, Gedye C, Bernardini MQ, Neel BG, Ailles LE (2011) Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells. Proc Natl Acad Sci 108(16):6468–6473CrossRefGoogle Scholar
  20. 20.
    Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, Roberts DJ, Seiden MV, Scadden DT, Rueda BR, Foster R (2009) CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells 27(12):2875–2883PubMedGoogle Scholar
  21. 21.
    Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68(11):4311–4320CrossRefGoogle Scholar
  22. 22.
    Kwon MJ, Shin YK (2013) Regulation of ovarian cancer stem cells or tumor-initiating cells. Int J Mol Sci 14(4):6624–6648CrossRefGoogle Scholar
  23. 23.
    Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, Silasi DA, Steffensen KD, Waldstrom M, Visintin I, Mor G (2009) Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle 8(1):158–166CrossRefGoogle Scholar
  24. 24.
    Romero I, Bast RC Jr (2012) Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy. Endocrinology 153(4):1593–1602CrossRefGoogle Scholar
  25. 25.
    Gao MQ, Choi YP, Kang S, Youn JH, Cho NH (2010) CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene 29(18):2672–2680CrossRefGoogle Scholar
  26. 26.
    Shah MM, Landen CN (2014) Ovarian cancer stem cells: are they real and why are they important? Gynecol Oncol 132(2):483–489CrossRefGoogle Scholar
  27. 27.
    Ho CM, Chang SF, Hsiao CC, Chien TY, Shih DT (2012) Isolation and characterization of stromal progenitor cells from ascites of patients with epithelial ovarian adenocarcinoma. J Biomed Sci 19(1):23Google Scholar
  28. 28.
    Yang L, Lai D (2013) Ovarian cancer stem cells enrichment. Methods Mol Biol 1049:337-345 Google Scholar
  29. 29.
    Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT, Donahoe PK (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci USA 103(30):11154-11159Google Scholar
  30. 30.
    Kenda Suster N, Virant-Klun I (2019) Presence and role of stem cells in ovarian cancer. World J Stem Cells 11(7):383-397 Google Scholar
  31. 31.
    Terraneo N, Jacob F, Dubrovska A, Grünberg J (2020) Novel therapeutic strategies for ovarian cancer stem cells. Front Oncol 10:319 Google Scholar
  32. 32.
    Peng S, Maihle NJ, Huang Y (2010) Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene 29(14):2153-2159 Google Scholar
  33. 33.
    Cole JM, Joseph S, Sudhahar CG, Cowden Dahl KD (2014) Enrichment for chemoresistant ovarian cancer stem cells from human cell lines. J Vis Exp (91):51891Google Scholar
  34. 34.
    Silva IA, Bai S, McLean K, Yang K, Griffith K, Thomas D, Ginestier C, Johnston C, Kueck A, Reynolds RK, Wicha MS (2011) Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res 71(11):3991–4001Google Scholar
  35. 35.
    Ahmed N, Abubaker K, Findlay J, Quinn M (2010) Epithelial mesenchymal transition and cancer stem cell-like phenotypes facilitate chemoresistance in recurrent ovarian cancer. Curr Cancer Drug Targets 10(3):268–278Google Scholar
  36. 36.
    Chen W, Dong J, Haiech J, Kilhoffer MC, Zeniou M (2016) Cancer stem cell quiescence and plasticity as major challenges in cancer therapy. Stem Cells Int 2016:1Google Scholar
  37. 37.
    Lupia M, Cavallaro U (2017) Ovarian cancer stem cells: still an elusive entity? Mol Cancer 16(1):64Google Scholar
  38. 38.
    McAuliffe SM, Morgan SL, Wyant GA, Tran LT, Muto KW, Chen YS, Chin KT, Partridge JC, Poole BB, Cheng KH, Daggett J (2012) Targeting notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc Natl Acad Sci 109(43):E2939–E2948Google Scholar
  39. 39.
    Zhang T, Xu J, Deng S, Zhou F, Li J, Zhang L, Li L, Wang QE, Li F (2018) Core signaling pathways in ovarian cancer stem cell revealed by integrative analysis of multi-marker genomics data. PLoS One 13(5):e0196351CrossRefGoogle Scholar
  40. 40.
    Ray A, Meng E, Reed E, Shevde LA, Rocconi RP (2011) Hedgehog signaling pathway regulates the growth of ovarian cancer spheroid forming cells. Int J Oncol 39(4):797–804Google Scholar
  41. 41.
    Chen Q, Gao G, Luo S (2013) Hedgehog signaling pathway and ovarian cancer. Chin J Cancer Res 25(3):346Google Scholar
  42. 42.
    Cao L, Shao M, Schilder J, Guise T, Mohammad KS, Matei D (2012) Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer. Oncogene 31(20):2521–2534Google Scholar
  43. 43.
    Wiese KE, Nusse R, van Amerongen R (2018) Wnt signalling: conquering complexity. Development 145(12):dev165902Google Scholar
  44. 44.
    Lan L, Luo Y, Cui D, Shi BY, Deng W, Huo LL, Chen HL, Zhang GY, Deng LL (2013) Epithelial-mesenchymal transition triggers cancer stem cell generation in human thyroid cancer cells. Int J Oncol 43(1):113–120Google Scholar
  45. 45.
    Espada J, Calvo MB, Díaz-Prado S, Medina V (2009) Wnt signalling and cancer stem cells. Clin Transl Oncol 11(7):411–427Google Scholar
  46. 46.
    Ramachandran I, Thavathiru E, Ramalingam S, Natarajan G, Mills WK, Benbrook DM, Zuna R, Lightfoot S, Reis A, Anant S, Queimado L (2012) Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo. Oncogene 31(22):2725–2737CrossRefGoogle Scholar
  47. 47.
    Ramachandran I, Ganapathy V, Gillies E, Fonseca I, Sureban SM, Houchen CW, Reis A, Queimado L (2014) Wnt inhibitory factor 1 suppresses cancer stemness and induces cellular senescence. Cell Death Dis 5(5):e1246CrossRefGoogle Scholar
  48. 48.
    Nusse R, Clevers H (2017) Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 169(6):985–999Google Scholar
  49. 49.
    Anastas JN, Moon RT (2013) WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer 13(1):11–26Google Scholar
  50. 50.
    Arend RC, Londoño-Joshi AI, Straughn JM Jr, Buchsbaum DJ (2013) The Wnt/β-catenin pathway in ovarian cancer: a review. Gynecol Oncol 131(3):772–779Google Scholar
  51. 51.
    Su HY, Lai HC, Lin YW, Liu CY, Chen CK, Chou YC, Lin SP, Lin WC, Lee HY, Yu MH (2010) Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway. Int J Cancer 127(3):555–567Google Scholar
  52. 52.
    Gatcliffe TA, Monk BJ, Planutis K, Holcombe RF (2008) Wnt signaling in ovarian tumorigenesis. Int J Gynecol Cancer 18(5):954–962Google Scholar
  53. 53.
    Wu R, Zhai Y, Fearon ER, Cho KR (2001) Diverse mechanisms of β-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res 61(22):8247–8255Google Scholar
  54. 54.
    Groeneweg JW, Foster R, Growdon WB, Verheijen RH, Rueda BR (2014) Notch signaling in serous ovarian cancer. J Ovarian Res 7(1):95Google Scholar
  55. 55.
    Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, Yang SX, Ivy SP (2015) Targeting notch, hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 12(8):445Google Scholar
  56. 56.
    Rose SL, Kunnimalaiyaan M, Drenzek J, Seiler N (2010) Notch 1 signaling is active in ovarian cancer. Gynecol Oncol 117(1):130–133Google Scholar
  57. 57.
    Chiaramonte R, Colombo M, Bulfamante G, Falleni M, Tosi D, Garavelli S, De Simone D, Vigolo E, Todoerti K, Neri A, Platonova N (2015) Notch pathway promotes ovarian cancer growth and migration via CXCR4/SDF1α chemokine system. Int J Biochem Cell Biol 66:134–140Google Scholar
  58. 58.
    Xie Q, Cheng Z, Chen X, Lobe CG, Liu J (2017) The role of notch signalling in ovarian angiogenesis. J Ovarian Res 10(1):13Google Scholar
  59. 59.
    Hopfer O, Zwahlen D, Fey MF, Aebi S (2005) The notch pathway in ovarian carcinomas and adenomas. Br J Cancer 93(6):709–718Google Scholar
  60. 60.
    Schmid S, Bieber M, Zhang F, Zhang M, He B, Jablons D, Teng NN (2011) Wnt and hedgehog gene pathway expression in serous ovarian cancer. Int J Gynecol Cancer 21(6):975–980Google Scholar
  61. 61.
    Liao X, Siu MK, Au CW, Wong ES, Chan HY, Ip PP, Ngan HY, Cheung AN (2009) Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 30(1):131–140Google Scholar
  62. 62.
    Chang WH, Lai AG (2019) Aberrations in notch-hedgehog signalling reveal cancer stem cells harbouring conserved oncogenic properties associated with hypoxia and immunoevasion. Br J Cancer 16:1–3Google Scholar
  63. 63.
    Roane BM, Arend RC, Birrer MJ (2019) Targeting the transforming growth factor-beta pathway in ovarian cancer. Cancer 11(5):668Google Scholar
  64. 64.
    Alsina-Sanchís E, Figueras A, Lahiguera A, Gil-Martín M, Pardo B, Piulats JM, Martí L, Ponce J, Matias-Guiu X, Vidal A, Villanueva A (2017) TGFβ controls ovarian cancer cell proliferation. Int J Mol Sci 18(8):1658Google Scholar
  65. 65.
    Yeung TL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, Zaid TM, Ghosh S, Birrer MJ, Mok SC (2013) TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res 73(16):5016–5028Google Scholar
  66. 66.
    Xia Y, Shen S, Verma IM (2014) NF-κB, an active player in human cancers. Cancer Immunol Res 2(9):823–830Google Scholar
  67. 67.
    Taniguchi K, Karin M (2018) NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 18(5):309–324Google Scholar
  68. 68.
    Harrington BS, Annunziata CM (2019) NF-κB signaling in ovarian cancer. Cancer 11(8):1182Google Scholar
  69. 69.
    Hernandez L, Hsu SC, Davidson B, Birrer MJ, Kohn EC, Annunziata CM (2010) Activation of NF-κB signaling by inhibitor of NF-κB kinase β increases aggressiveness of ovarian cancer. Cancer Res 70(10):4005–4014Google Scholar
  70. 70.
    Alvero AB (2010) Recent insights into the role of NF-kappaB in ovarian carcinogenesis. Genome Med 2(8):56Google Scholar
  71. 71.
    House CD, Jordan E, Hernandez L, Ozaki M, James JM, Kim M, Kruhlak MJ, Batchelor E, Elloumi F, Cam MC, Annunziata CM (2017) NFκB promotes ovarian tumorigenesis via classical pathways that support proliferative cancer cells and alternative pathways that support ALDH+ cancer stem–like cells. Cancer Res 77(24):6927–6940Google Scholar
  72. 72.
    Ottevanger PB (2017) Ovarian cancer stem cells more questions than answers. Semin Cancer Biol 44:67–71Google Scholar
  73. 73.
    Steffensen KD, Alvero AB, Yang Y, Waldstrøm M, Hui P, Holmberg JC, Silasi DA, Jakobsen A, Rutherford T, Mor G (2011) Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer. J Oncol 2011:1Google Scholar
  74. 74.
    Rizzo S, Hersey JM, Mellor P, Dai W, Santos-Silva A, Liber D, Luk L, Titley I, Carden CP, Box G, Hudson DL (2011) Ovarian cancer stem cell–like side populations are enriched following chemotherapy and overexpress EZH2. Mol Cancer Ther 10(2):325–335Google Scholar
  75. 75.
    Keyvani V, Farshchian M, Esmaeili SA, Yari H, Moghbeli M, Nezhad SR, Abbaszadegan MR (2019) Ovarian cancer stem cells and targeted therapy. J Ovarian Res 12(1):120Google Scholar
  76. 76.
    Zong X, Nephew KP (2019) Ovarian cancer stem cells: role in metastasis and opportunity for therapeutic targeting. Cancer 11(7):934Google Scholar
  77. 77.
    Kim J, Gosnell JE, Roman SA (2019) Geographic influences in the global rise of thyroid cancer. Nat Rev Endocrinol 15:1–3Google Scholar
  78. 78.
    Wang TS, Sosa JA (2018) Thyroid surgery for differentiated thyroid cancer—recent advances and future directions. Nat Rev Endocrinol 14(11):670–683Google Scholar
  79. 79.
    Zhang P, Zuo H, Ozaki T, Nakagomi N, Kakudo K (2006) Cancer stem cell hypothesis in thyroid cancer. Pathol Int 56(9):485–489Google Scholar
  80. 80.
    Lin RY (2011) Thyroid cancer stem cells. Nat Rev Endocrinol 7(10):609Google Scholar
  81. 81.
    Nagayama Y, Shimamura M, Mitsutake N (2016) Cancer stem cells in the thyroid. Front Endocrinol 7:20Google Scholar
  82. 82.
    Hardin H, Zhang R, Helein H, Buehler D, Guo Z, Lloyd RV (2017) The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors. Lab Invest 97(10):1142–1151Google Scholar
  83. 83.
    Shimamura M, Nagayama Y, Matsuse M, Yamashita S, Mitsutake N (2014) Analysis of multiple markers for cancer stem-like cells in human thyroid carcinoma cell lines. Endocr J 61(5):481–490Google Scholar
  84. 84.
    Mahmood NA, Tawfeeq AT, Al-Sudani IM, Abd-Alghni ZS (2019) Rationales for the use of cancer stem cells markers in the staging of papillary thyroid carcinoma. J Oncol 2019:1659654Google Scholar
  85. 85.
    Vicari L, Colarossi C, Giuffrida D, De Maria R, Memeo L (2016) Cancer stem cells as a potential therapeutic target in thyroid carcinoma. Oncol Lett 12(4):2254–2260Google Scholar
  86. 86.
    Jiye YI, Jianting ZH (2011) Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application. Zhong Nan Da Xue Xue Bao Yi Xue Ban 36(10):927Google Scholar
  87. 87.
    Zheng X, Cui D, Xu S, Brabant G, Derwahl M (2010) Doxorubicin fails to eradicate cancer stem cells derived from anaplastic thyroid carcinoma cells: characterization of resistant cells. Int J Oncol 37(2):307–315Google Scholar
  88. 88.
    Carina V, Zito G, Pizzolanti G, Richiusa P, Criscimanna A, Rodolico V, Tomasello L, Pitrone M, Arancio W, Giordano C (2013) Multiple pluripotent stem cell markers in human anaplastic thyroid cancer: the putative upstream role of SOX2. Thyroid 23(7):829–837Google Scholar
  89. 89.
    Ma R, Minsky N, Morshed SA, Davies TF (2014) Stemness in human thyroid cancers and derived cell lines: the role of asymmetrically dividing cancer stem cells resistant to chemotherapy. J Clin Endocrinol Metab 99(3):E400Google Scholar
  90. 90.
    Malaguarnera R, Belfiore A (2014) The emerging role of insulin and insulin-like growth factor signaling in cancer stem cells. Front Endocrinol 5:10Google Scholar
  91. 91.
    Hardin H, Montemayor-Garcia C, Lloyd RV (2013) Thyroid cancer stem-like cells and epithelial-mesenchymal transition in thyroid cancers. Hum Pathol 44(9):1707–1713Google Scholar
  92. 92.
    Arufe MC, Lu M, Lin RY (2009) Differentiation of murine embryonic stem cells to thyrocytes requires insulin and insulin-like growth factor-1. Biochem Biophys Res Commun 381(2):264–270Google Scholar
  93. 93.
    Maiorano E, Ciampolillo A, Viale G, Maisonneuve P, Ambrosi A, Triggiani V, Marra E, Perlino E (2000) Insulin-like growth factor 1 expression in thyroid tumors. Appl Immunohistochem Mol Morphol 8(2):110–119Google Scholar
  94. 94.
    Heiden KB, Williamson AJ, Doscas ME, Ye J, Wang Y, Liu D, Xing M, Prinz RA, Xu X (2014) The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression. J Clin Endocrinol Metabol 99(11):E2178–E2187Google Scholar
  95. 95.
    Dong W, Cui J, Tian X, He L, Wang Z, Zhang P, Zhang H (2014) Aberrant sonic hedgehog signaling pathway and STAT3 activation in papillary thyroid cancer. Int J Clin Exp Med 7(7):1786Google Scholar
  96. 96.
    Williamson AJ, Doscas ME, Ye J, Heiden KB, Xing M, Li Y, Prinz RA, Xu X (2016) The sonic hedgehog signaling pathway stimulates anaplastic thyroid cancer cell motility and invasiveness by activating Akt and c-Met. Oncotarget 7(9):10472Google Scholar
  97. 97.
    Venkatesh V, Nataraj R, Thangaraj GS, Karthikeyan M, Gnanasekaran A, Kaginelli SB, Kuppanna G, Kallappa CG, Basalingappa KM (2018) Targeting notch signalling pathway of cancer stem cells. Stem Cell Investig 5:5Google Scholar
  98. 98.
    Geers C, Colin IM, Gérard AC (2011) Delta-like 4/notch pathway is differentially regulated in benign and malignant thyroid tissues. Thyroid 21(12):1323–1330Google Scholar
  99. 99.
    Ferretti E, Tosi E, Po A, Scipioni A, Morisi R, Espinola MS, Russo D, Durante C, Schlumberger M, Screpanti I, Filetti S, Gulino A (2008) Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors. J Clin Endocrinol Metab 93(10):4080–4087Google Scholar
  100. 100.
    Vasko V, Espinosa AV, Scouten W, He H, Auer H, Liyanarachchi S, Larin A, Savchenko V, Francis GL, de la Chapelle A, Saji M, Ringel MD (2007) Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion. Proc Natl Acad Sci U S A 104(8):2803–2808Google Scholar
  101. 101.
    Yamashita AS, Geraldo MV, Fuziwara CS, Kulcsar MA, Friguglietti CU, da Costa RB, Baia GS, Kimura ET (2013) Notch pathway is activated by MAPK signaling and influences papillary thyroid cancer proliferation. Transl Oncol 6(2):197Google Scholar
  102. 102.
    Shiraiwa K, Matsuse M, Nakazawa Y, Ogi T, Suzuki K, Saenko V, Xu S, Umezawa K, Yamashita S, Tsukamoto K, Mitsutake N (2019) JAK/STAT3 and NF-κB signaling pathways regulate cancer stem-cell properties in anaplastic thyroid cancer cells. Thyroid 29(5):674–682Google Scholar
  103. 103.
    Xing M (2013) Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 13(3):184–199Google Scholar
  104. 104.
    Ahn SH, Henderson YC, Williams MD, Lai SY, Clayman GL (2014) Detection of thyroid cancer stem cells in papillary thyroid carcinoma. J Clin Endocrinol Metabol 99(2):536–544Google Scholar
  105. 105.
    Hombach-Klonisch S, Natarajan S, Thanasupawat T, Medapati MR, Pathak A, Ghavami S, Klonisch T (2014) Mechanisms of therapeutic resistance in cancer (stem) cells with emphasis on thyroid cancer cells. Front Endocrinol 5:37Google Scholar
  106. 106.
    Chen G, Nicula D, Renko K, Derwahl MI (2015) Synergistic anti-proliferative effect of metformin and sorafenib on growth of anaplastic thyroid cancer cells and their stem cells. Oncol Rep 33(4):1994–2000Google Scholar
  107. 107.
    Naoum GE, Morkos M, Kim B, Arafat W (2018) Novel targeted therapies and immunotherapy for advanced thyroid cancers. Mol Cancer 17(1):51Google Scholar
  108. 108.
    Perri F, Di Lorenzo G, Scarpati GD, Buonerba C (2011) Anaplastic thyroid carcinoma: a comprehensive review of current and future therapeutic options. World J Clin Oncol 2(3):150Google Scholar
  109. 109.
    Khatami F, Larijani B, Nikfar S, Hasanzad M, Fendereski K, Tavangar SM (2019) Personalized treatment options for thyroid cancer: current perspectives. Pharmacogenom Pers Med 12:235Google Scholar
  110. 110.
    Viola D, Valerio L, Molinaro E, Agate L, Bottici V, Biagini A, Lorusso L, Cappagli V, Pieruzzi L, Giani C, Sabini E (2016) Treatment of advanced thyroid cancer with targeted therapies: ten years of experience. Endocr Relat Cancer 23(4):R185–R205Google Scholar
  111. 111.
    Valerio L, Pieruzzi L, Giani C, Agate L, Bottici V, Lorusso L, Cappagli V, Puleo L, Matrone A, Viola D, Romei C (2017) Targeted therapy in thyroid cancer: state of the art. Clin Oncol 29(5):316–324Google Scholar
  112. 112.
    Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65(20):9328–9337Google Scholar
  113. 113.
    Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451(7176):345–349Google Scholar
  114. 114.
    Held MA, Curley DP, Dankort D, McMahon M, Muthusamy V, Bosenberg MW (2010) Characterization of melanoma cells capable of propagating tumors from a single cell. Cancer Res 70(1):388–397Google Scholar
  115. 115.
    Nguyen N, Couts KL, Luo Y, Fujita M (2015) Understanding melanoma stem cells. Melanoma Manag 2(2):179–188Google Scholar
  116. 116.
    Boiko AD, Razorenova OV, van de Rijn M, Swetter SM, Johnson DL, Ly DP, Butler PD, Yang GP, Joshua B, Kaplan MJ, Longaker MT (2010) Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature 466(7302):133–137Google Scholar
  117. 117.
    Parmiani G (2016) Melanoma cancer stem cells: markers and functions. Cancer 8(3):34Google Scholar
  118. 118.
    Brinckerhoff CE (2017) Cancer stem cells (CSCs) in melanoma: There’s smoke, but is there fire? J Cell Physiol 232(10):2674–2678Google Scholar
  119. 119.
    Rosenberg SA, Restifo NP (2015) Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348(6230):62–68Google Scholar
  120. 120.
    Kumar D, Gorain M, Kundu G, Kundu GC (2017) Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma. Mol Cancer 16(1):7Google Scholar
  121. 121.
    Escobar SG, Chin MH, Sandberg ML, Xu H (2017) Isolation and characterization of a distinct subpopulation from the WM115 cell line that resembles in vitro properties of melanoma cancer stem cells. SLAS Discov 22(5):484–493PubMedGoogle Scholar
  122. 122.
    Tirino V, Desiderio V, Paino F, De Rosa A, Papaccio F, La Noce M, Laino L, De Francesco F, Papaccio G (2013) Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization. FASEB J 27(1):13–24CrossRefGoogle Scholar
  123. 123.
    Slipicevic A, Somasundaram R, Sproesser K, Herlyn M (2014) Isolation of melanoma cell subpopulations using negative selection. Methods Mol Biol 1102:501–512CrossRefGoogle Scholar
  124. 124.
    Geng L, Cuneo KC, Cooper MK, Wang H, Sekhar K, Fu A, Hallahan DE (2007) Hedgehog signaling in the murine melanoma microenvironment. Angiogenesis 10(4):259–267Google Scholar
  125. 125.
    Santini R, Vinci MC, Pandolfi S, Penachioni JY, Montagnani V, Olivito B, Gattai R, Pimpinelli N, Gerlini G, Borgognoni L, Stecca B (2012) Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells. Stem Cells 30(9):1808–1818Google Scholar
  126. 126.
    Pandolfi S, Montagnani V, Lapucci A, Stecca B (2015) HEDGEHOG/GLI-E2F1 axis modulates iASPP expression and function and regulates melanoma cell growth. Cell Death Differ 22(12):2006–2019Google Scholar
  127. 127.
    Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434(7035):843–850Google Scholar
  128. 128.
    Kumar D, Kumar S, Gorain M, Tomar D, Patil HS, Radharani NN, Kumar TV, Patil TV, Thulasiram HV, Kundu GC (2016) Notch1-MAPK signaling axis regulates CD133+ cancer stem cell-mediated melanoma growth and angiogenesis. J Investig Dermatol 136(12):2462–2474Google Scholar
  129. 129.
    Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284(5415):770–776Google Scholar
  130. 130.
    Kaushik G, Venugopal A, Ramamoorthy P, Standing D, Subramaniam D, Umar S, Jensen RA, Anant S, Mammen JM (2015) Honokiol inhibits melanoma stem cells by targeting notch signaling. Mol Carcinog 54(12):1710–1721Google Scholar
  131. 131.
    Lin X, Sun B, Zhu D, Zhao X, Sun R, Zhang Y, Zhang D, Dong X, Gu Q, Li Y, Liu F (2016) Notch4+ cancer stem-like cells promote the metastatic and invasive ability of melanoma. Cancer Sci 107(8):1079–1091Google Scholar
  132. 132.
    Schlegel NC, von Planta A, Widmer DS, Dummer R, Christofori G (2015) PI 3K signalling is required for a TGF β-induced epithelial–mesenchymal-like transition (EMT-like) in human melanoma cells. Exp Dermatol 24(1):22–28Google Scholar
  133. 133.
    Calvani M, Bianchini F, Taddei ML, Becatti M, Giannoni E, Chiarugi P, Calorini L (2016) Etoposide-Bevacizumab a new strategy against human melanoma cells expressing stem-like traits. Oncotarget 7(32):51138Google Scholar
  134. 134.
    Hovinga KE, Shimizu F, Wang R, Panagiotakos G, Van Der Heijden M, Moayedpardazi H, Correia AS, Soulet D, Major T, Menon J, Tabar V (2010) Inhibition of notch signaling in glioblastoma targets cancer stem cells via an endothelial cell intermediate. Stem Cells 28(6):1019–1029Google Scholar
  135. 135.
    Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, Piccirillo S, Vescovi AL, DiMeco F, Olivi A, Eberhart CG (2007) Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells 25(10):2524–2533Google Scholar
  136. 136.
    Curtin JC, Lorenzi MV (2010) Drug discovery approaches to target Wnt signaling in cancer stem cells. Oncotarget 1(7):563Google Scholar
  137. 137.
    Wróbel S, Przybyło M, Stępień E (2019) The clinical trial landscape for melanoma therapies. J Clin Med 8(3):368CrossRefGoogle Scholar
  138. 138.
    Wang YB, Lv G, Xu FH, Ma LL, Yao YM (2020) Comprehensive survey of clinical trials registration for melanoma immunotherapy in the clinicaltrials.gov. Front Pharmacol 10:1539CrossRefGoogle Scholar
  139. 139.
    Li C, Lee CJ, Simeone DM (2009) Identification of human pancreatic cancer stem cells. Methods Mol Biol 568:161–173Google Scholar
  140. 140.
    Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323Google Scholar
  141. 141.
    Ercan G, Karlitepe A, Ozpolat B (2017) Pancreatic cancer stem cells and therapeutic approaches. Anticancer Res 37(6):2761–2775Google Scholar
  142. 142.
    Bao Q, Zhao Y, Renner A, Niess H, Seeliger H, Jauch KW, Bruns CJ (2010) Cancer stem cells in pancreatic cancer. Cancer 2(3):1629–1641Google Scholar
  143. 143.
    Wang HC, Hou YC, Shan YS (2014) Advances in pancreatic cancer stem cells, tumor-associated macrophages, and their interplay. Cancer Cell Microenviron 1:e304Google Scholar
  144. 144.
    Rasheed Z, Wang Q, Matsui W (2010) Isolation of stem cells from human pancreatic cancer xenografts. J Vis Exp (43):2169Google Scholar
  145. 145.
    Gzil A, Zarębska I, Bursiewicz W, Antosik P, Grzanka D, Szylberg Ł (2019) Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Mol Biol Rep 46(6):6629–6645CrossRefGoogle Scholar
  146. 146.
    Giovannetti E, van der Borden CL, Frampton AE, Ali A, Firuzi O, Peters GJ (2017) Never let it go: stopping key mechanisms underlying metastasis to fight pancreatic cancer. Semin Cancer Biol 44:43–59Google Scholar
  147. 147.
    Subramaniam D, Kaushik G, Dandawate P, Anant S (2018) Targeting cancer stem cells for chemoprevention of pancreatic cancer. Curr Med Chem 25(22):2585–2594Google Scholar
  148. 148.
    Honselmann KC, Pross M, Jung CM, Wellner UF, Deichmann S, Keck T, Bausch D (2015) Regulation mechanisms of the hedgehog pathway in pancreatic cancer: a review. J Pancreas 16(1):25–32Google Scholar
  149. 149.
    Lee CJ, Dosch J, Simeone DM (2008) Pancreatic cancer stem cells. J Clin Oncol 26(17):2806–2812CrossRefGoogle Scholar
  150. 150.
    Onishi H, Katano M (2014) Hedgehog signaling pathway as a new therapeutic target in pancreatic cancer. World J Gastroenterol: WJG 20(9):2335Google Scholar
  151. 151.
    Ponnurangam S, Dandawate PR, Dhar A, Tawfik OW, Parab RR, Mishra PD, Ranadive P, Sharma R, Mahajan G, Umar S, Weir SJ (2016) Quinomycin A targets notch signaling pathway in pancreatic cancer stem cells. Oncotarget 7(3):3217Google Scholar
  152. 152.
    Rumman M, Jung KH, Fang Z, Yan HH, Son MK, Kim SJ, Kim J, Park JH, Lim JH, Hong S, Hong SS (2016) HS-173, a novel PI3K inhibitor suppresses EMT and metastasis in pancreatic cancer. Oncotarget 7(47):78029Google Scholar
  153. 153.
    Saygin C, Matei D, Majeti R, Reizes O, Lathia JD (2019) Targeting cancer stemness in the clinic: from hype to hope. Cell Stem Cell 24(1):25–40Google Scholar
  154. 154.
    Seufferlein T, Ettrich TJ (2019) Treatment of pancreatic cancer-neoadjuvant treatment in resectable pancreatic cancer (PDAC). Transl Gastroenterol Hepatol 4:21CrossRefGoogle Scholar
  155. 155.
    Pu N, Lou W, Yu J (2019) PD-1 immunotherapy in pancreatic cancer: current status. J Pancreatology 2(1):6–10CrossRefGoogle Scholar
  156. 156.
    Yamakawa K, Nakano-Narusawa Y, Hashimoto N, Yokohira M, Matsuda Y (2019) Development and clinical trials of nucleic acid medicines for pancreatic cancer treatment. Int J Mol Sci 20(17):4224CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Gautham Chengizkhan
    • 1
  • Bharti Bisht
    • 2
  • Sridhar Muthusami
    • 3
    • 4
  • Muralidharan Anbalagan
    • 5
  • Ilangovan Ramachandran
    • 1
    • 6
  • R. Ileng Kumaran
    • 7
    Email author
  1. 1.Department of Endocrinology, Dr. ALM PG Institute of Basic Medical SciencesUniversity of Madras, Taramani CampusChennaiIndia
  2. 2.Lung Cancer Research Program, Division of Thoracic Surgery, David Geffen School of Medicine, UCLA Jonsson Comprehensive Cancer CenterUniversity of CaliforniaLos AngelesUSA
  3. 3.Department of BiochemistryKarpagam Academy of Higher EducationCoimbatoreIndia
  4. 4.Karpagam Cancer Research CentreKarpagam Academy of Higher EducationCoimbatoreIndia
  5. 5.Department of Structural and Cellular Biology, Louisiana Cancer Research CenterTulane UniversityNew OrleansUSA
  6. 6.Department of Obstetrics and Gynecology, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  7. 7.Biology DepartmentFarmingdale State CollegeFarmingdaleUSA

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